Dynamic nuclear polarization (DNP) is used to enhance the nuclear polarization of samples for use in applications such as nuclear magnetic resonance (NMR) analysis including nuclear magnetic resonance imaging (MRI) and analytical high-resolution NMR spectroscopy (MRS). MRI is a diagnostic technique that has become particularly attractive to physicians as it is non-invasive and does not involve exposing the patient under study to potentially harmful radiation such as X-rays. Analytical high resolution NMR spectroscopy is routinely used in the determination of molecular structure.
MRI and NMR spectroscopy lack sensitivity due to the normally very low polarization of the nuclear spins of the materials used. In view of this, the dynamic nuclear polarization technique has been developed to improve the polarization of nuclear spins.
In a typical DNP process, a liquid sample is mixed with a polarising agent and placed in a sample cup which is mounted to a sample holding tube. The sample holding tube is then inserted into the bore of a superconducting magnet located in a cryostat so as to bring the sample to a working volume within the bore, the working volume being located in a microwave cavity defined by a DNP insert. The superconducting magnet generates a magnetic field of suitable strength and homogeneity in the working volume.
The sample is cooled and solidified by exposing it to liquid helium in the bore and then irradiated with microwaves while it is exposed to the magnetic field and in its frozen state. The sample is then lifted out of the liquid helium to a position in which it is still subject to the magnetic field although this may be less homogeneous. Hot solvent is then supplied into the sample holding tube, typically through a dissolution tube or stick or other solvent conveying system, to the working volume so as to dissolve the polarised sample. Alternatively, the sample may be melted. The solution or melt is then rapidly extracted and transferred for subsequent use for analysis in an NMR system.
At present there are two approaches that have become commercially available in the last few years. In a first approach, as also described above, dissolution DNP is applied. In this method, a paramagnetic radical molecule is mixed with the sample, frozen and cooled down to for instance 2 K. Using microwave irradiation for a time up to several hours, the electron spin polarization is transferred to the molecule under study. The sample is then quickly dissolved, heated to room temperature and transferred to the NMR system, where a single or few scan NMR analysis is performed with superior sensitivity. In another approach, Magic Angle Spinning (MAS) solid state DNP, the sample remains in the solid phase, at a temperature of about 90 K. Using high-resolution MAS-NMR, the samples can be studied in situ.
US2008/290869 describes an apparatus for performing in-vitro DNP-NMR measurements on a sample comprising a magnetic field generating apparatus located in a cryostat and surrounding a bore defining respective NMR and DNP working regions. A system for performing DNP on a suitably prepared sample in the DNP working region is also mentioned. A system for performing a NMR process on a sample in the NMR working region is also mentioned. A sample positioning mechanism which can be inserted in the bore to bring a sample in turn into each of the working regions is also mentioned. The magnetic field generating apparatus is structured so that the magnetic field in the DNP working region has a homogeneity or profile suitable for performing DNP on the sample and the magnetic field in the NMR working region has a homogeneity or profile suitable for performing a NMR process on the sample.
Bart et al, Journal of Magnetic Resonance, vol. 201, no. 2, 1 Dec. 2009, pages 175-185, reports on the optimization, fabrication and experimental characterization of a stripline-based microfluidic NMR probe, realized in a silicon substrate. The stripline geometry was modelled in respect of rf-homogeneity, sensitivity and spectral resolution. The fabrication of the chip is described.
US2005/0122115 describes an electromagnetic field sensor or generator employing a radio frequency micro strip transmission channel formed by a low-loss dielectric substrate sandwiched between a non-resonant micro strip conductor. A discontinuity in said micro strip conductor that substantially alters its cross-sectional dimensions causes electrical signals in the micro strip conductor to be inductively coupled to near field electromagnetic radiation in the vicinity of the discontinuity. The discontinuity may be defined by one or more holes, slots, slits or stubs in the micro strip. The sensor/generator may be used in numerous applications, including NMR spectrometry, as a near field scanning device to inspect operating integrated circuits, or to read or write data on magnetic materials.
EP2146215 describes an apparatus having a magnet arrangement for producing magnetic field in a working volume. The magnet arrangement produces a control field with magnetic field gradients of high orders in a direction of an axis in a working volume. A compensation arrangement of magnetic material is positioned in the latter working volume. The magnetic field gradients of high orders range between −90% and −110% of magnetic field gradients of same orders of the control field of the magnet arrangement in the direction of the axis in the latter volume. Also a method for aligning a compensation arrangement made of magnetic material is described.
WO9613735 describes that an NMR probe positions a flow chamber with first and second flow regions in the high field of an NMR apparatus. A second, downstream, flow region is surrounded by an exciter/detector coil which may be of a conventional type for home- or hetero nuclear detection, while an upstream, first region is excited by an antenna to condition or enhance a downstream measurement. The downstream coil is tuned to detect hetero nuclear resonances, while the upstream coil may be tuned for enhancement of the same or a different species. A cavity, in conjunction with the upstream coil, allows populations and transfer coherence excitation between electrons and nuclei.
US20090051361 describes a coolant sub-assembly for use in a DNP apparatus. The sub-assembly comprises a plurality of concentric jackets surrounding an inner bore tube having first and second opposed ends. The jackets are adapted to inhibit heat flow to the inner bore tube, a DNP working region being defined within the inner bore tube where a DNP process will be performed on a sample in the DNP working region. A coolant supply path extends adjacent an outer surface of the inner bore tube at the DNP working region in order to cool said outer surface, whereby a sample holder assembly can be inserted through the first end of the inner bore tube to bring a sample holder into the DNP working region and can be moved through the second end of the inner bore tube. An auxiliary coolant supply path supplies coolant to a sample, located in use in the sample holder at the DNP working region, through at least one aperture in the inner bore tube wall at the DNP working region. One or both ends of the inner bore tube opens into a coolant waste path for conveying coolant away from the inner bore tube, and wherein the coolant, auxiliary coolant, and waste paths are coupled to pumping means in use to cause coolant to pass along the coolant, auxiliary coolant and waste paths.
J. A. Gardeniers et al., Transducers 2009, Denver, Colo., USA, Jun. 21-25, 2009, W2B.001, pages 1642-1645, describes a silicon-based microfluidic chip with an integrated RF stripline for NMR detection, with high spectral resolution (ca. 1 Hz at 600 MHZ proton resonance) and high sensitivity (ca. 1.2 mM) for mass-limited (600 nL) biological samples, with a particular focus on human cerebrospinal fluid samples.